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Positions
- Associate Professor; Director of Radiation Biology Research & Education
- Radiation Oncology
- Baylor College of Medicine
- Houston, Texas, United States
- Assistant Professor
- Houston Methodist Research Institute
- Postdoctoral Scientist
- Medicine
- Cardiovascular Medicine
- Stanford University
- Member
- Dan L Duncan Comprehensive Cancer Center
- Baylor College of Medicine
- Houston, Texas, United States
Education
- PhD from University of Cape Town
Honors & Awards
- Fellow of the American Heart Association
Professional Statement
Regulation of the nitric oxide synthase (NOS) pathway using small molecules is a major strategy we employ in my laboratory to translate basic research insights into useful therapy for cardiovascular and pulmonary diseases. Recently, we applied high throughput screening (HTS) technology to discover small molecules that directly regulate this pathway. Intriguingly, we discovered that proton pump inhibitors (PPIs; a class of FDA-approved drug developed to treat gastric acidity) directly modulate the NOS pathway and regulate many of the downstream processes associated with overly active NOS including tissue inflammation and fibrosis.
More recently, we demonstrated that PPIs suppress lung inflammation and fibrosis in an experimental model of acute lung injury in part by regulating the transcription of inducible NOS (iNOS) and several classic pro-inflammatory cytokines.
Currently, we have ongoing cardiovascular and pulmonary projects that leverage our strength in pharmacology:
Cardiovascular: Our projects include modulation of the vascular endothelial system using small molecules and microRNA to treat cardiovascular disease including atherosclerosis.
Pulmonary: We are working towards developing stand-alone and combinatorial therapy to modulate lung inflammation and fibrosis that results from chemical (e.g. bleomycin) or ionizing radiation.
Selected Publications
- Ghebre YT, Raghu G.. "Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drug." Am J Respir Crit Care Med.. 2016 April 25 Pubmed PMID: 27110898
- Ghebremariam YT, Cooke JP, Gerhart W, Griego C, Brower JB, Doyle-Eisele M, Moeller BC, Zhou Q, Ho L, de Andrade J, Raghu G, Peterson L, Rivera A, Rosen GD.. "Pleiotropic effect of the proton pump inhibitor esomeprazole leading to suppression of lung inflammation and fibrosis.." J Transl Med.. 2015 August 1;13:249. Pubmed PMID: 26231702
- Zhou G, Meng S, Li Y, Ghebre YT, Cooke JP.. "Optimal ROS Signaling Is Critical for Nuclear Reprogramming.." Cell Rep.. 2016 May 3;15(5):919-925. Pubmed PMID: 27117405
- Lai L, Ghebremariam YT.. "Modulating DDAH/NOS Pathway to Discover Vasoprotective Insulin Sensitizers.." J Diabetes Res.. 2016 December 6;2016:1982096. Pubmed PMID: 26770984
- Sukhovershin RA, Yepuri G, Ghebremariam YT.. "Endothelium-Derived Nitric Oxide as an Antiatherogenic Mechanism: Implications for Therapy.." Methodist DeBakey Cardiovasc J.. 2015 September;11(3):166-171. Pubmed PMID: 26634024
- Sukhovershin RA, Ghebremariam YT, Cooke JP.. "Lansoprazole worsens asthma control in poor metabolizers: is nitric oxide involved?." Ann Am Thorac Soc.. 2015 July;12(7):1109-1110.. Pubmed PMID: 26203616
- Shah NH, LePendu P, Bauer-Mehren A, Ghebremariam YT, Iyer SV, Marcus J, Nead KT, Cooke JP, Leeper NJ.. "Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.." PLoS One.. 2015 June 10;10(6):e0124653.. Pubmed PMID: 26061035
- Ghebremariam YT, Cooke JP, Khan F, Thakker RN, Chang P, Shah NH, Nead KT, Leeper NJ.. "Proton pump inhibitors and vascular function: A prospective cross-over pilot study.." Vasc Med.. 2015 August;20(4):309-316.. Pubmed PMID: 25835348
- Ghebremariam YT, Lee JC, LePendu P, Erlanson DA, Slaviero A, Shah NH, Leiper JM, Cooke JP.. "Response to letters regarding article, "unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine".." Circulation.. 2014 April 1;129(13):e428.. Pubmed PMID: 24687654
- Ghebremariam YT, Huang NF, Kambhampati S, Volz KS, Joshi GG, Anslyn EV, Cooke JP.. "Characterization of a fluorescent probe for imaging nitric oxide.." J Vasc Res.. 2014;51(1):68-79.. Pubmed PMID: 24335468
- Lependu P, Iyer SV, Bauer-Mehren A, Harpaz R, Ghebremariam YT, Cooke JP, Shah NH.. "Pharmacovigilance using Clinical Text.." AMIA Jt Summits Transl Sci Proc.. 2013 March 18;2013:109. Pubmed PMID: 24303315
- Ghebremariam YT, Erlanson DA, Cooke JP.. "A novel and potent inhibitor of dimethylarginine dimethylaminohydrolase: a modulator of cardiovascular nitric oxide.." J Pharmacol Exp Ther.. 2014 January;348(1):69-76.. Pubmed PMID: 24135074
- Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, Leiper J, Cooke JP.. "Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine.." Circulation.. 2013 August 20;128(8):845-853.. Pubmed PMID: 23825361
- Ghebremariam YT, Yamada K, Lee JC, Johnson CL, Atzler D, Anderssohn M, Agrawal R, Higgins JP, Patterson AJ, Böger RH, Cooke JP.. "FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats.." PLoS One.. 2013 April 4;8(4):e60653.. Pubmed PMID: 23593273
- White MP, Rufaihah AJ, Liu L, Ghebremariam YT, Ivey KN, Cooke JP, Srivastava D.. "Limited gene expression variation in human embryonic stem cell and induced pluripotent stem cell-derived endothelial cells.." Stem Cells.. 2013 January;31(1):92-103.. Pubmed PMID: 23079999
- Ghebremariam YT, Erlanson DA, Yamada K, Cooke JP.. "Development of a dimethylarginine dimethylaminohydrolase (DDAH) assay for high-throughput chemical screening.." J Biomol Screen.. 2012 June;17(5):651-661.. Pubmed PMID: 22460174
- Cooke JP, Ghebremariam YT.. "DDAH says NO to ADMA.." Arterioscler Thromb Vasc Biol.. 2011 July;31(7):1462-1464.. Pubmed PMID: 21677286
- Cooke JP, Ghebremariam YT.. "Dietary nitrate, nitric oxide, and restenosis.." J Clin Invest.. 2011 April;121(4):1258-1260.. Pubmed PMID: 21436578
- Yang WC, Patel KG, Lee J, Ghebremariam YT, Wong HE, Cooke JP, Swartz JR.. "Cell-free production of transducible transcription factors for nuclear reprogramming.." Biotechnol Bioeng.. 2009 December 15;104(6):1047-1058.. Pubmed PMID: 19718703
- Ghebremariam YT, Engelbrecht G, Tyler M, Lotz Z, Govender D, Kotwal GJ, Kahn D.. "Vaccinia virus complement control protein (VCP) improves kidney structure and function following ischemia/reperfusion injury in rats.." J Surg Res.. 2010 April;159(2):747-754.. Pubmed PMID: 19691975
- Cooke JP, Ghebremariam YT.. "Endothelial nicotinic acetylcholine receptors and angiogenesis.." Trends Cardiovasc Med.. 2008 October;18(7):247-253.. Pubmed PMID: 19232953
- Thorgersen EB, Ghebremariam YT, Thurman JM, Fung M, Nielsen EW, Holers VM, Kotwal GJ, Mollnes TE.. "Candidate inhibitors of porcine complement.." Mol Immunol.. 2007 March;44(8):1827-1834.. Pubmed PMID: 17109963
- Kotwal GJ, Kaczmarek JN, Leivers S, Ghebremariam YT, Kulkarni AP, Bauer G, De Beer C, Preiser W, Mohamed AR.. "Anti-HIV, anti-poxvirus, and anti-SARS activity of a nontoxic, acidic plant extract from the Trifollium species Secomet-V/anti-vac suggests that it contains a novel broad-spectrum antiviral.." Ann N Y Acad Sci.. 2005 November;1056:293-302.. Pubmed PMID: 16387696
- Ghebremariam YT, Smith SA, Anderson JB, Kahn D, Kotwal GJ.. "Intervention strategies and agents mediating the prevention of xenorejection.." Ann N Y Acad Sci.. 2005 November;1056:123-143.. Pubmed PMID: 16387682
- Ghebremariam YT, Odunuga OO, Janse K, Kotwal GJ.. "Humanized recombinant vaccinia virus complement control protein (rVCP) with three amino acid changes is 100-fold more active than wildtype rVCP in blocking both classical and alternative complement pathways.." Ann N Y Acad Sci.. 2005 November;1056:113-122.. Pubmed PMID: 16387681
- Kulkarni AP, Ghebremariam YT, Kotwal GJ.. "Curcumin inhibits the classical and the alternate pathways of complement activation.." Ann N Y Acad Sci.. 2005 November;1056:100-112.. Pubmed PMID: 16387680
- Yohannes T Ghebre. "Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: flip side of the story." Inflammation & Cell Signaling. 2016 September;3(2)
- Yohannes T Ghebre*, Eduard Yakubov, Wing Tak Wong, Prasanna Krishnamurthy, Nazish Sayed, Andrew G Sikora and Mark D Bonnen. "Vascular Aging: Implications for Cardiovascular Disease and Therapy." Translational Medicine. 2016 September;6:183.
- Yohannes T Ghebre, Ganesh Raghu. "Proton pump inhibitors in IPF: beyond mere suppression of gastric acidity." QJM: An International Journal of Medicine. 2016 September;109(9):577-579.
- Nelson C, Lee J, Ko K, Sikora AG, Bonnen MD, Enkhbaatar P, Ghebre YT. "Therapeutic Efficacy of Esomeprazole in Cotton Smoke-Induced Lung Injury Model." Front Pharmacol.. 2017 January 26;8:16. Pubmed PMID: 28184197
- Ghebre YT. "Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: flip side of the story." Inflamm Cell Signal.. 2016;3(3):pii: e1397. Pubmed PMID: 29302606
- Ghebre YT. "Proton Pump Inhibitors in IPF: A Call for Clinical Trials." Front Pharmacol.. 2018 May 17;9:499. Pubmed PMID: 29867501
- Pham N, Bonnen MD, Ghebre YT. "Silent Neoplastic Cardiac Invasion in Small Cell Lung Cancer: A Case Report and Review of the Literature." Am J Case Rep.. 2018 May 30;19:619-622. Pubmed PMID: 29844305
- Li L, Mok H, Jhaveri P, Bonnen MD, Sikora AG, Eissa NT, Komaki RU, Ghebre YT. "Anticancer therapy and lung injury: molecular mechanisms." Expert Rev Anticancer Ther.. 2018 July 23;23:1-17. Pubmed PMID: 29996062
Memberships
- American Thoracic Society
- American Heart Association
Funding
- DDAH As a Novel Target in Pulmonary Fibrosis
- Grant funding from NIH (NHLBI)
Intellectual Property
- Dimethylarginine Dimethylaminohydrolase Inhibitors and Methods of Use Thereof
- Use of small molecules including proton pump inhibitors (PPIs) to modulate lung remodeling.